severe combined immunodeficiency

Summary

Summary: Group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. It is inherited as an X-linked or autosomal recessive defect. Mutations occurring in many different genes cause human SCID.

Top Publications

  1. ncbi LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
    S Hacein-Bey-Abina
    INSERM Unit 429, Cedex 15, France
    Science 302:415-9. 2003
  2. ncbi Gene therapy for immunodeficiency due to adenosine deaminase deficiency
    Alessandro Aiuti
    San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
    N Engl J Med 360:447-58. 2009
  3. ncbi Highly efficient endogenous human gene correction using designed zinc-finger nucleases
    Fyodor D Urnov
    Sangamo BioSciences, Inc, Pt Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nature 435:646-51. 2005
  4. pmc Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases
    Tomoji Mashimo
    Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    PLoS ONE 5:e8870. 2010
  5. pmc Efficacy of gene therapy for X-linked severe combined immunodeficiency
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Necker Enfants Malades Hospital, Paris, France
    N Engl J Med 363:355-64. 2010
  6. pmc Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Universite Rene Descartes, Paris, France
    J Clin Invest 118:3132-42. 2008
  7. ncbi Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency
    A Puel
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    Nat Genet 20:394-7. 1998
  8. ncbi Generation and characterization of severe combined immunodeficiency rats
    Tomoji Mashimo
    Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Cell Rep 2:685-94. 2012
  9. pmc Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients
    Steven J Howe
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, University College London, London, United Kingdom
    J Clin Invest 118:3143-50. 2008
  10. ncbi Il2rg gene-targeted severe combined immunodeficiency pigs
    Shunichi Suzuki
    Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305 0901, Japan
    Cell Stem Cell 10:753-8. 2012

Detail Information

Publications285 found, 100 shown here

  1. ncbi LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1
    S Hacein-Bey-Abina
    INSERM Unit 429, Cedex 15, France
    Science 302:415-9. 2003
    We have previously shown correction of X-linked severe combined immunodeficiency [SCID-X1, also known as gamma chain (gamma(c)) deficiency] in 9 out of 10 patients by retrovirus-mediated gamma(c) gene transfer into autologous CD34 bone ..
  2. ncbi Gene therapy for immunodeficiency due to adenosine deaminase deficiency
    Alessandro Aiuti
    San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
    N Engl J Med 360:447-58. 2009
    We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency.
  3. ncbi Highly efficient endogenous human gene correction using designed zinc-finger nucleases
    Fyodor D Urnov
    Sangamo BioSciences, Inc, Pt Richmond Tech Center 501, Canal Blvd, Suite A100 Richmond, California 94804, USA
    Nature 435:646-51. 2005
    ..We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease...
  4. pmc Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID) using zinc-finger nucleases
    Tomoji Mashimo
    Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    PLoS ONE 5:e8870. 2010
    ..Recently, zinc-finger nucleases (ZFNs) were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc...
  5. pmc Efficacy of gene therapy for X-linked severe combined immunodeficiency
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Necker Enfants Malades Hospital, Paris, France
    N Engl J Med 363:355-64. 2010
    ..We reviewed long-term outcomes after gene therapy in nine patients with X-linked severe combined immunodeficiency (SCID-X1), which is characterized by the absence of the cytokine receptor common gamma chain.
  6. pmc Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1
    Salima Hacein-Bey-Abina
    Department of Biotherapy, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris AP HP, Universite Rene Descartes, Paris, France
    J Clin Invest 118:3132-42. 2008
    ..Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer...
  7. ncbi Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency
    A Puel
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1674, USA
    Nat Genet 20:394-7. 1998
    b>Severe combined immunodeficiency (SCID) is caused by multiple genetic defects. The most common form of SCID, X-linked SCID (XSCID), results from mutations in IL2RG (ref...
  8. ncbi Generation and characterization of severe combined immunodeficiency rats
    Tomoji Mashimo
    Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    Cell Rep 2:685-94. 2012
    b>Severe combined immunodeficiency (SCID) mice, the most widely used animal model of DNA-PKcs (Prkdc) deficiency, have contributed enormously to our understanding of immunodeficiency, lymphocyte development, and DNA-repair mechanisms, and ..
  9. pmc Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients
    Steven J Howe
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, University College London, London, United Kingdom
    J Clin Invest 118:3143-50. 2008
    ....
  10. ncbi Il2rg gene-targeted severe combined immunodeficiency pigs
    Shunichi Suzuki
    Transgenic Animal Research Center, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305 0901, Japan
    Cell Stem Cell 10:753-8. 2012
    A porcine model of severe combined immunodeficiency (SCID) promises to facilitate human cancer studies, the humanization of tissue for xenotransplantation, and the evaluation of stem cells for clinical therapy, but SCID pigs have not been ..
  11. ncbi Reduced central tolerance in Omenn syndrome leads to immature self-reactive oligoclonal T cells
    Raz Somech
    Cancer Research Center, Safra Children s Hospital, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv, Israel
    J Allergy Clin Immunol 124:793-800. 2009
    ..Dysregulations of the central and peripheral immune tolerance, mediated by the protein autoimmune regulator (AIRE) and regulatory T cells, respectively, were proposed as possible mechanisms of this aberrant inflammatory process...
  12. ncbi Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation
    T Blunt
    Wellcome Cancer Research Campaign Institute, Cambridge University, England
    Cell 80:813-23. 1995
    ..As DNA-PK binds to DNA ends and is activated by these structures, our findings provide novel insights into V(D)J recombination and DNA repair processes...
  13. ncbi Severe combined immunodeficiency. A model disease for molecular immunology and therapy
    Alain Fischer
    INSERM U429, Hopital Necker Enfants Malades, Paris, France
    Immunol Rev 203:98-109. 2005
    ..SCID is thus a disease model for experimental therapy in the hematopoietic system...
  14. ncbi Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy
    Salima Hacein-Bey-Abina
    Laboratoire INSERM, Hopital Necker Enfants Malades, Paris, France
    N Engl J Med 346:1185-93. 2002
    X-linked severe combined immunodeficiency due to a mutation in the gene encoding the common gamma (gamma(c)) chain is a lethal condition that can be cured by allogeneic stem-cell transplantation...
  15. ncbi Radiosensitive SCID patients with Artemis gene mutations show a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow
    Jeroen G Noordzij
    Department of Immunology, Erasmus MC University Medical Center Rotterdam, The Netherlands
    Blood 101:1446-52. 2003
    b>Severe combined immunodeficiency disease (SCID) can be immunologically classified by the absence or presence of T, B, and natural killer (NK) cells...
  16. ncbi [Gene therapy of severe combined immunodeficiency disease: proof of principle of efficiency and safety issues. Gene therapy, primary immunodeficiencies, retrovirus, lentivirus, genome]
    Alain Fischer
    INSERM U 429, Unité d Immunologie et Hématologie Pédiatrique et Département de Biothérapie, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris
    Bull Acad Natl Med 189:779-85; discussion 786-8. 2005
    ..Vector modifications, based mostly on inactivating the enhancer activity of the LTR, should preserve efficacy while improving safety...
  17. ncbi Direct cytopathic effects of particular hepatitis B virus genotypes in severe combined immunodeficiency transgenic with urokinase-type plasminogen activator mouse with human hepatocytes
    Masaya Sugiyama
    Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    Gastroenterology 136:652-62.e3. 2009
    ..We investigate HBV genotype-related differences in viral replication, antigen expression, and histopathology in severe combined immunodeficiency transgenic with urokinase-type plasminogen activator mice harboring human hepatocytes.
  18. pmc Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes
    Rebecca H Buckley
    Departments of Pediatrics and Immunology, Duke University Medical Center, Box 2898 or 363 Jones Building, Durham, NC 27710, USA
    Immunol Res 49:25-43. 2011
    b>Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T- and B-cell function and, in some types, also of NK cells and function...
  19. ncbi Gene therapy for primary immunodeficiencies: Part 2
    Alessandro Aiuti
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Division of Regenerative Medicine, San Raffaele Scientific Institute, Milan, Italy
    Curr Opin Immunol 24:585-91. 2012
    ..In this review we present the status of gene therapy for WAS and CGD, and discuss the emerging application of similar strategies to a broader range of PIDs, such as IPEX syndrome...
  20. ncbi Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR
    Stephan Borte
    Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
    Blood 119:2552-5. 2012
    b>Severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) are inborn errors of immune function that require prompt diagnosis and treatment to prevent life-threatening infections...
  21. ncbi Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy
    Barbara Cassani
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Milan, Italy
    Blood 114:3546-56. 2009
    ..We evaluated the genomic impact of RV integration in T lymphocytes from adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) patients 10 to 30 months after infusion of autologous, genetically corrected CD34(+) cells...
  22. ncbi A critical role for IL-21 in regulating immunoglobulin production
    Katsutoshi Ozaki
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892 1674, USA
    Science 298:1630-4. 2002
    ..all share the common cytokine receptor gamma chain, gammac, which is mutated in humans with X-linked severe combined immunodeficiency disease (XSCID)...
  23. ncbi Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development
    S M Russell
    Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute NHLBI, National Institutes of Health NIH, Bethesda, MD 20892, USA
    Science 270:797-800. 1995
    Males with X-linked severe combined immunodeficiency (XSCID) have defects in the common cytokine receptor gamma chain (gamma c) gene that encodes a shared, essential component of the receptors of interleukin-2 (IL-2), IL-4, IL-7, IL-9, ..
  24. ncbi Severe combined immunodeficiency and microcephaly in siblings with hypomorphic mutations in DNA ligase IV
    Dietke Buck
    INSERM, Hopital Necker Enfants Malades, U429, Unité Développement Normal et Pathologique du Système Immunitaire, Paris, France
    Eur J Immunol 36:224-35. 2006
    ..These observations contrast with the severity of the clinical immunodeficiency, suggesting that Lig4 may have additional critical roles in lymphocyte survival beyond V(D)J recombination...
  25. ncbi More than just SCID--the phenotypic range of combined immunodeficiencies associated with mutations in the recombinase activating genes (RAG) 1 and 2
    Tim Niehues
    HELIOS Klinikum Krefeld, Center for Child and Adolescent Health, Krefeld, Germany
    Clin Immunol 135:183-92. 2010
    ..Thorough assessment and interpretation of clinical and immunological findings will guide treatment modalities as intense as hematopoietic stem cell transplantation...
  26. pmc Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness
    Chantal Lagresle-Peyrou
    Research Laboratory on Normal and Pathologic Development of the Immune System, U768, Institut National de la Sante et de la Recherche Medicale, 75015 Paris, France
    Nat Genet 41:106-11. 2009
    Reticular dysgenesis is an autosomal recessive form of human severe combined immunodeficiency characterized by an early differentiation arrest in the myeloid lineage and impaired lymphoid maturation...
  27. pmc Integration profile of retroviral vector in gene therapy treated patients is cell-specific according to gene expression and chromatin conformation of target cell
    Luca Biasco
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Milano, Italy
    EMBO Mol Med 3:89-101. 2011
    ..same therapeutic moloney murine leukemia virus (MLV) vector in the context of the adenosine deaminase-severe combined immunodeficiency (ADA-SCID) genetic background in two GT trials based on infusions of transduced mature lymphocytes (..
  28. pmc Increased hydrophobicity at the N terminus/membrane interface impairs gating of the severe combined immunodeficiency-related ORAI1 mutant
    Isabella Derler
    Institute for Biophysics, University of Linz, Altenbergerstrasse 69, 4040 Linz, Austria
    J Biol Chem 284:15903-15. 2009
    ..In conclusion, the increase in hydrophobicity at the N terminus/membrane interface represents the major cause for yielding non-functional ORAI1 channels...
  29. ncbi Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency
    Benedicte Neven
    Unité d Immuno Hématologie et Rhumatologie Pédiatrique, Hopital Necker Enfants Malades, Assistance Publique Hopitaux de Paris, Paris, France
    Blood 113:4114-24. 2009
    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for severe combined immunodeficiency (SCID)...
  30. ncbi Long-term therapy with aerosolized ribavirin for parainfluenza 3 virus respiratory tract infection in an infant with severe combined immunodeficiency
    Jitka Stankova
    Division of Hematology and Oncology, Montreal Children s Hospital, McGill University Health Centre, Montreal, QC, Canada
    Pediatr Transplant 11:209-13. 2007
    We report the case of an infant with severe combined immunodeficiency who was presented with PIV3 infection...
  31. pmc Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice
    T Hudcovic
    Institute of Microbiology of Academy of Sciences of Czech Republic, v v i, Prague, Czech Republic
    Clin Exp Immunol 167:356-65. 2012
    ..Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C...
  32. ncbi Calcium signalling in lymphocyte activation and disease
    Stefan Feske
    Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA
    Nat Rev Immunol 7:690-702. 2007
    ....
  33. ncbi Cognitive and behavioral abnormalities in children after hematopoietic stem cell transplantation for severe congenital immunodeficiencies
    Penny Titman
    Department of Psychosocial Services, Great Ormond Street Hospital National Health Service NHS Trust, London, UK
    Blood 112:3907-13. 2008
    ..analysis indicated that the underlying genetic defect, diagnosis of adenosine deaminase-deficient severe combined immunodeficiency, and consanguinity were associated with worse outcome but that age at transplantation and ..
  34. pmc Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction
    Denise A Carbonaro
    Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles UCLA, Los Angeles, CA 90095, USA
    Blood 120:3677-87. 2012
    ..In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist...
  35. pmc Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome
    Francesca Rucci
    Division of Immunology and Manton Center for Orphan Disease Research, Children s Hospital Boston, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:3024-9. 2010
    ..These findings highlight the importance of LIG4 in lymphocyte development and function, and in genomic stability maintenance, and provide a model for the complex phenotype of LIG4 syndrome in humans...
  36. ncbi Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency
    Amel Hassan
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, United Kingdom
    Blood 120:3615-24; quiz 3626. 2012
    ..These data detail for the first time the outcomes of HCT for ADA-SCID and show that, if patients survive HCT, long-term cellular and humoral immune recovery is achieved...
  37. pmc Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency
    Kiho Lee
    Division of Animal Science
    Proc Natl Acad Sci U S A 111:7260-5. 2014
    Pigs with severe combined immunodeficiency (SCID) may provide useful models for regenerative medicine, xenotransplantation, and tumor development and will aid in developing therapies for human SCID patients...
  38. pmc Correction of canine X-linked severe combined immunodeficiency by in vivo retroviral gene therapy
    Suk See Ting-De Ravin
    Laboratory of Host Defenses, NIAID, NIH, Building 10 CRC, Room 5 3750, 10 Center Drive, Bethesda, MD 20892 1456, USA
    Blood 107:3091-7. 2006
    X-linked severe combined immunodeficiency (XSCID) is characterized by profound immunodeficiency and early mortality, the only potential cure being hematopoietic stem cell (HSC) transplantation or gene therapy...
  39. ncbi Gene therapy for severe combined immunodeficiency
    Marina Cavazzana-Calvo
    Département de Biothérapie, Hopital Necker Enfants Malades, 75015 Paris, France
    Annu Rev Med 56:585-602. 2005
    Studies of severe combined immunodeficiency (SCID), a group of rare monogenic disorders, have provided key findings about the physiology of immune system development...
  40. ncbi Ancestral founder mutation of the nude (FOXN1) gene in congenital severe combined immunodeficiency associated with alopecia in southern Italy population
    M Adriani
    Department of Pediatrics, Federico II University, Naples, Italy
    Ann Hum Genet 68:265-8. 2004
    ..The three haplotypes identified, 3/R255X/3, 3/R255X/2 and 3/R255X/1, are consistent with a single ancestral origin for the mutation R255X...
  41. ncbi Targeted disruption of the Artemis murine counterpart results in SCID and defective V(D)J recombination that is partially corrected with bone marrow transplantation
    Lanying Li
    Department of Pediatrics, University of California, San Francisco, CA 94143, USA
    J Immunol 174:2420-8. 2005
    ....
  42. ncbi Matched unrelated bone marrow transplant for T+ combined immunodeficiency
    C M Roifman
    Division of Immunology and Allergy, The Hospital for Sick Children, Ontario, Canada ickkids ca
    Bone Marrow Transplant 41:947-52. 2008
    ..We have shown here that matched unrelated donor BMT is highly effective in curing patients with T+ CID. This mode of treatment should be preferred for patients with T+ CID when a related identical donor is not available...
  43. ncbi Detection of RAG mutations and prenatal diagnosis in families presenting with either T-B- severe combined immunodeficiency or Omenn's syndrome
    U Tabori
    Pediatric Hematology Oncology, Safra Children s Hospital, Sheba Medical Center, Tel Hashomer, Israel
    Clin Genet 65:322-6. 2004
    ..the recombination activating genes RAG1 and RAG2 are involved in each of the two different types of severe combined immunodeficiency (SCID) syndromes: T-B- SCID and Omenn's syndrome (OS)...
  44. pmc A novel missense RAG-1 mutation results in T-B-NK+ SCID in Athabascan-speaking Dine Indians from the Canadian Northwest Territories
    Zheng Xiao
    Pediatric Bone Marrow Transplant Division, University of California San Francisco Children s Hospital, San Francisco, CA 94143 1278, USA
    Eur J Hum Genet 17:205-12. 2009
    ..Defective NHEJ and subsequent failure of V(D)J recombination leads to severe combined immunodeficiency disease (SCID)...
  45. ncbi A novel IL2RG mutation associated with maternal T lymphocyte engraftment in a patient with severe combined immunodeficiency
    Richard Kellermayer
    Department of Medical Genetics and Child Development, University of Pecs, József A u 7, 7623, Pecs, Hungary
    J Hum Genet 51:495-7. 2006
    b>Severe combined immunodeficiency (SCID) represents a genetically heterogeneous group of primary immunodeficiency disorders...
  46. pmc Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans
    Fabio Candotti
    Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health NIH, Bethesda, MD, USA
    Blood 120:3635-46. 2012
    We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells...
  47. ncbi Lack of nonfunctional B-cell receptor rearrangements in a patient with normal B cell numbers despite partial RAG1 deficiency and atypical SCID/Omenn syndrome
    Line Ohm-Laursen
    Department of Clinical Immunology, Odense University Hospital, 5000 Odense, Denmark
    J Clin Immunol 28:588-92. 2008
    ..A 2.5-month old boy presented with recurrent wheezing, protracted diarrhea, erythrodermia, and failure to thrive...
  48. pmc Short stature in partially corrected X-linked severe combined immunodeficiency--suboptimal response to growth hormone
    Suk See De Ravin
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases NIAID, Bethesda, MD 20892, USA
    J Pediatr Endocrinol Metab 21:1057-63. 2008
    X-linked severe combined immunodeficiency (XSCID) results from defects in the common cytokine receptor gamma chain (gamma c) required for signaling by receptors for interleukin (IL)-2, -4, -7, -9, -15, and -21...
  49. ncbi FOXN1 mutation abrogates prenatal T-cell development in humans
    I Vigliano
    Department of Pediatrics, Federico II University, Via Pansini, 5, Naples 80131, Italy
    J Med Genet 48:413-6. 2011
    ....
  50. pmc Laboratory technology for population-based screening for severe combined immunodeficiency in neonates: the winner is T-cell receptor excision circles
    Jennifer M Puck
    Division of Allergy, Immunology and Bone Marrow Transplantation, Department of Pediatrics, University of California San Francisco, San Francisco, CA 94143 0519, USA
    J Allergy Clin Immunol 129:607-16. 2012
    The most profound primary immunodeficiency disease, severe combined immunodeficiency (SCID), is fatal in infancy unless affected infants are provided with an adaptive immune system through allogeneic hematopoietic cell transplantation, ..
  51. ncbi Gene therapy for severe combined immunodeficiency due to adenosine deaminase deficiency
    Claudia A Montiel-Equihua
    Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, 30, Guilford Street, London WC1N 1EH, UK
    Curr Gene Ther 12:57-65. 2012
    The severe combined immunodeficiency caused by the absence of adenosine deaminase (SCID-ADA) was the first monogenic disorder for which gene therapy was developed...
  52. pmc The long quest for neonatal screening for severe combined immunodeficiency
    Rebecca H Buckley
    Departments of Pediatrics and Immunology, Duke University Medical Center, Durham, NC 27710, USA
    J Allergy Clin Immunol 129:597-604; quiz 605-6. 2012
    Early recognition of severe combined immunodeficiency (SCID) is a pediatric emergency because a diagnosis before live vaccines or nonirradiated blood products are given and before development of infections permits lifesaving ..
  53. pmc A human severe combined immunodeficiency (SCID) condition with increased sensitivity to ionizing radiations and impaired V(D)J rearrangements defines a new DNA recombination/repair deficiency
    N Nicolas
    Institut National de la Santé et de la Recherche Médicale U429, Developpement Normal et Pathologique du Systeme Immunitaire, Hopital Necker Enfants Malades, 75015 Paris, France
    J Exp Med 188:627-34. 1998
    ..of in vitro mutants (Chinese hamster ovary cells) and in vivo situations of murine and equine severe combined immunodeficiency (scid)...
  54. ncbi High-throughput multiplexed T-cell-receptor excision circle quantitative PCR assay with internal controls for detection of severe combined immunodeficiency in population-based newborn screening
    Jacalyn L Gerstel-Thompson
    New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain, MA 02130, USA
    Clin Chem 56:1466-74. 2010
    ..detects the absence of functional T cells and has a demonstrated clinical validity for detecting severe combined immunodeficiency (SCID) in infants...
  55. ncbi Identification of severe combined immunodeficiency by T-cell receptor excision circles quantification using neonatal guthrie cards
    Yoichi Morinishi
    Department of Pediatrics, National Defense Medical College, Saitama, Japan
    J Pediatr 155:829-33. 2009
    To assess the feasibility of T-cell receptor excision circles (TRECs) quantification for neonatal mass screening of severe combined immunodeficiency (SCID).
  56. ncbi Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency
    Francesca Ferrua
    San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
    Curr Opin Allergy Clin Immunol 10:551-6. 2010
    The present review describes the recent progress in the treatment of adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) using autologous gene-modified hematopoietic stem cells, comparing immune reconstitution with ..
  57. ncbi Immune reconstitution in ADA-SCID after PBL gene therapy and discontinuation of enzyme replacement
    Alessandro Aiuti
    Nat Med 8:423-5. 2002
  58. ncbi B-cell recovery after stem cell transplantation of Artemis-deficient SCID requires elimination of autologous bone marrow precursor-B-cells
    Mirjam van der Burg
    Department of Immunology, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
    Haematologica 91:1705-9. 2006
    ..Apparently, occupation of the precursor-B-cell niches is a potential dominant factor influencing repopulation of a functional B-cell compartment in B-negative SCID...
  59. ncbi Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common gammac cytokine receptor subunit or JAK-3 deficiency
    Caroline Laffort
    Unite d immunologie, d Hématologie, et de Rhumatologie Pédiatrique, Paris, France
    Lancet 363:2051-4. 2004
    ..That genetic causes are the only predisposing factor to be identified for severe combined immune deficiency, suggests that natural-killer cells or gammac/JAK-3-dependent signalling in keratinocytes could have a role in anti-HPV immunity...
  60. ncbi Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies
    C Diaz de Heredia
    Department of Paediatric Haematology and Oncology, Hospital Vall d Hebron, Barcelona, Spain
    Bone Marrow Transplant 41:627-33. 2008
    ..No patient is intravenous immunoglobulin (IVIg) replacement therapy-dependent. UCB transplantation is a valid option for children with PID who lack an HLA-identical sibling donor...
  61. ncbi A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency
    Salima Hacein-Bey-Abina
    N Engl J Med 348:255-6. 2003
  62. ncbi Simultaneous quantification of recent thymic T-cell and bone marrow B-cell emigrants in patients with primary immunodeficiency undergone to stem cell transplantation
    Alessandra Sottini
    Diagnostics Department, Spedali Civili di Brescia, Brescia, Italy
    Clin Immunol 136:217-27. 2010
    ..In other patients, TRECs and KRECs number remained very low for the entire period of study...
  63. pmc Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients
    Barbara Cassani
    San Raffaele Telethon Institute for Gene Therapy, Milan, Italy
    Blood 111:4209-19. 2008
    Mutations in the adenosine deaminase (ADA) gene are responsible for a form of severe combined immunodeficiency (SCID) caused by the lymphotoxic accumulation of ADA substrates, adenosine and 2'-deoxy-adenosine...
  64. ncbi Systematic evidence review of newborn screening and treatment of severe combined immunodeficiency
    Ellen A Lipstein
    Center for Child and Adolescent Health Policy, Mass General Hospital for Children, Boston, Massachusetts, USA
    Pediatrics 125:e1226-35. 2010
    b>Severe combined immunodeficiency (SCID) is a group of disorders that leads to early childhood death as a result of severe infections. Recent research has addressed potential newborn screening for SCID.
  65. ncbi Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency
    Jose A Borghans
    Department of Immunology, University Medical Center Utrecht, The Netherlands
    Blood 108:763-9. 2006
    The immune system of patients with severe combined immunodeficiency (SCID) reconstitutes to a large extent during the first years after hematopoietic stem cell transplantation (HSCT)...
  66. pmc Long-term clinical outcome of patients with severe combined immunodeficiency who received related donor bone marrow transplants without pretransplant chemotherapy or post-transplant GVHD prophylaxis
    Mary Dell Railey
    Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA
    J Pediatr 155:834-840.e1. 2009
    To determine long-term health benefits of nonablative bone marrow transplantation for severe combined immunodeficiency (SCID), we investigated our cohort of 161 related donor bone marrow-transplanted patients with SCID...
  67. pmc How I treat ADA deficiency
    H Bobby Gaspar
    Centre for Immunodeficiency, Molecular Immunology Unit, University College London Institute of Child Health, London, United Kingdom
    Blood 114:3524-32. 2009
    Adenosine deaminase deficiency is a disorder of purine metabolism leading to severe combined immunodeficiency (ADA-SCID). Without treatment, the condition is fatal and requires early intervention...
  68. ncbi Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival
    Laurie A Myers
    Duke University Medical Center, Durham, NC 27710, USA
    Blood 99:872-8. 2002
    All genetic types of severe combined immunodeficiency (SCID) can be cured by stem cell transplantation from related donors...
  69. ncbi Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2
    Ulrich Pannicke
    Institute for Transfusion Medicine, University of Ulm, Ulm, Germany
    Nat Genet 41:101-5. 2009
    ..These observations suggest that reticular dysgenesis is the first example of a human immunodeficiency syndrome that is causally linked to energy metabolism and that can therefore be classified as a mitochondriopathy...
  70. ncbi Human equivalent of the mouse Nude/SCID phenotype: long-term evaluation of immunologic reconstitution after bone marrow transplantation
    C Pignata
    Department of Pediatrics and Cellular and Molecular Biology and Pathology, Federico II University, Naples, Italy
    Blood 97:880-5. 2001
    Human Nude/SCID (severe combined immunodeficiency) is the first severe combined immunodeficiency caused by mutation of the winged-helix-nude (WHN) gene, which is expressed in the thymus but not in the hematopoietic lineage...
  71. pmc A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells
    Sheng Zhou
    Division of Experimental Hematology, Department of Hematology, St Jude Children s Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA
    Blood 116:900-8. 2010
    To develop safer and more effective vectors for gene therapy of X-linked severe combined immunodeficiency (SCID-X1), we have evaluated new self-inactivating lentiviral vectors based on the HIV virus...
  72. ncbi Development of population-based newborn screening for severe combined immunodeficiency
    Kee Chan
    National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
    J Allergy Clin Immunol 115:391-8. 2005
    b>Severe combined immunodeficiency (SCID) is a treatable, inherited lack of cellular and humoral immunity caused by diverse mutations in several different genes and leading to death in infancy unless immune reconstitution is provided...
  73. ncbi Interleukin-7 receptor alpha (IL-7Ralpha) deficiency: cellular and molecular bases. Analysis of clinical, immunological, and molecular features in 16 novel patients
    Silvia Giliani
    Angelo Nocivelli Institute of Molecular Medicine, Department of Pediatrics, University of Brescia, Italy
    Immunol Rev 203:110-26. 2005
    Analysis of gene-targeted mice and patients with severe combined immunodeficiency due to mutations of the alpha chain of the interleukin-7 receptor (IL-7Ralpha) has shown important differences between mice and humans in the role played by ..
  74. ncbi Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chain
    K Ohbo
    Department of Microbiology, Tohoku University School of Medicine, Sendai, Japan
    Blood 87:956-67. 1996
    ..Mutations of the human gamma chain cause the X-linked severe combined immunodeficiency (XSCID), showing that T and natural killer cells absolutely require the gamma chain for their ..
  75. ncbi Development of a routine newborn screening protocol for severe combined immunodeficiency
    Mei W Baker
    Wisconsin State Laboratory of Hygiene, University of Wisconsin School of Medicine and Public Health, Madison, Wis 53706, USA
    J Allergy Clin Immunol 124:522-7. 2009
    b>Severe combined immunodeficiency (SCID) is characterized by the absence of functional T cells and B cells. Without early diagnosis and treatment, infants with SCID die from severe infections within the first year of life.
  76. pmc Reversible severe combined immunodeficiency phenotype secondary to a mutation of the proton-coupled folate transporter
    Arturo Borzutzky
    Division of Immunology, Children s Hospital Boston, Boston, MA, USA
    Clin Immunol 133:287-94. 2009
    ..PCFT mutations should be considered in infants with SCID-like phenotype, as the immunodeficiency is reversible with parenteral folinic acid repletion...
  77. ncbi Disseminated bacille Calmette-Guérin in Iranian children with severe combined immunodeficiency
    Mahnaz Sadeghi-Shabestari
    Division of Pediatric Immunology and Allergy, Children s Hospital, Tabriz University Medical Sciences, Tabriz, Iran
    Int J Infect Dis 13:e420-3. 2009
    ..This study was performed to determine the underlying defects in patients with BCG-osis...
  78. ncbi DNA-PKcs deficiency in human: long predicted, finally found
    Mirjam van der Burg
    Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
    Curr Opin Allergy Clin Immunol 9:503-9. 2009
    ..and molecular findings of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a new candidate gene for radiosensitive T-B-severe combined immunodeficiency (SCID), which has implications for the diagnostic strategy of T-B-SCID.
  79. pmc A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection
    Jean Pierre de Villartay
    Developpement Normal et Pathologique du Systeme Immunitaire, INSERM U429, Paris, France
    J Clin Invest 115:3291-9. 2005
    ..This observation extends the range of clinical and immunological phenotypes associated with RAG mutations, emphasizing the role of the genetic background and microbial environment in determining disease phenotype...
  80. ncbi Population-based newborn screening for severe combined immunodeficiency: steps toward implementation
    Jennifer M Puck
    Department of Pediatrics, University of California, San Francisco, CA 94143 0519, USA
    J Allergy Clin Immunol 120:760-8. 2007
    ....
  81. ncbi FOXN1 homozygous mutation associated with anencephaly and severe neural tube defect in human athymic Nude/SCID fetus
    S Amorosi
    Department of Pediatrics, Federico II University of Naples, Naples, Italy
    Clin Genet 73:380-4. 2008
    ..Alterations of the FOXN1 gene in both mice and humans result in a severe combined immunodeficiency caused by an intrinsic defect of the thymus associated with congenital alopecia (Nude/severe combined ..
  82. ncbi DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect
    C U Kirchgessner
    Department of Radiation Oncology, Stanford University School of Medicine, CA 94305
    Science 267:1178-83. 1995
    ..Chromosomal fragments expressing p350 complement the SCID phenotype, and p350 protein levels are greatly reduced in cells derived from SCID mice compared to cells from wild-type mice...
  83. ncbi Reduced thymic output, increased spontaneous apoptosis and oligoclonal B cells in polyethylene glycol-adenosine deaminase-treated patients
    Fabio Malacarne
    Department of Laboratory Diagnostics, Terzo Servizio Analisi, Spedali Civili of Brescia, Brescia, Italy
    Eur J Immunol 35:3376-86. 2005
    Impairment of purine metabolism due to adenosine deaminase (ADA) deficiency is associated with a severe combined immunodeficiency (SCID)...
  84. ncbi Purine nucleoside phosphorylase deficiency
    M L Markert
    Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710
    Immunodefic Rev 3:45-81. 1991
    ..PNP) deficiency is a rare inherited disease accounting for approximately 4% of patients with severe combined immunodeficiency. Thirty-three patients have been reported...
  85. ncbi A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation
    E K Shin
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA
    J Immunol 158:3565-9. 1997
    ....
  86. ncbi Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID)
    P Macchi
    Istituto di Tecnologie Biomediche Avanzate, Consiglio Nazionale delle Ricerche, Milano, Italy
    Nature 377:65-8. 1995
    ..Both mutations resulted in markedly reduced levels of Jak-3. These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans...
  87. ncbi RAG mutations in human B cell-negative SCID
    K Schwarz
    Section of Molecular Biology, University of Ulm, D 89070 Ulm, Germany
    Science 274:97-9. 1996
    Patients with human severe combined immunodeficiency (SCID) can be divided into those with B lymphocytes (B+ SCID) and those without (B- SCID)...
  88. ncbi Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution
    Rebecca H Buckley
    Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA
    Annu Rev Immunol 22:625-55. 2004
    Mutations in nine different genes have been found to cause the human severe combined immunodeficiency syndrome...
  89. ncbi Defective expression of the interleukin-2/interleukin-15 receptor beta subunit leads to a natural killer cell-deficient form of severe combined immunodeficiency
    K C Gilmour
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford St, London WC1N 1EH, UK
    Blood 98:877-9. 2001
    ..on cytokine signaling, and defects in cytokine receptor complex subunits have been shown to result in severe combined immunodeficiency (SCID) syndromes in humans and in murine models...
  90. ncbi Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease
    C Kung
    Howard Hughes Medical Institute, St Louis, Missouri 63110, USA
    Nat Med 6:343-5. 2000
    ..The patient presented at 2 months of age with severe combined immunodeficiency disease...
  91. ncbi Targeted disruption of the catalytic subunit of the DNA-PK gene in mice confers severe combined immunodeficiency and radiosensitivity
    G E Taccioli
    Department of Microbiology, Boston University School of Medicine, Massachusetts 02118, USA
    Immunity 9:355-66. 1998
    ..This suggests that the Scid mice may not represent a null phenotype and may retain some residual DNA-PKcs function...
  92. ncbi The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events
    Ulrich Pannicke
    Institute for Transfusion Medicine, University of Ulm, Ulm, Germany
    Hum Mutat 31:197-207. 2010
    ..mutations in the DCLRE1C gene, which encodes ARTEMIS, suffer from radiosensitive B(-/low) T(-/low) severe combined immunodeficiency (SCID) or radiosensitive Omenn syndrome...
  93. pmc Genetics of SCID
    Fausto Cossu
    Pediatric HSCT Unit, 2 Pediatric Clinic of University, Ospedale Microcitemico, Via Jenner s n, 09121 Cagliari, Sardinia, Italy
    Ital J Pediatr 36:76. 2010
    Human SCID (Severe Combined Immunodeficiency) is a prenatal disorder of T lymphocyte development, that depends on the expression of numerous genes. The knowledge of the genetic basis of SCID is essential for diagnosis (e.g...
  94. ncbi Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening
    Lucinda Brown
    Department of Clinical Immunology, Great Ormond Street Hospital National Health Service Trust, London, UK
    Blood 117:3243-6. 2011
    b>Severe combined immunodeficiency (SCID) carries a poor prognosis without definitive treatment by hematopoietic stem cell transplantation...
  95. ncbi Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications
    Manfred Hönig
    Department of Pediatrics, University of Ulm, University Clinic for Child and Adolescent Medicine, Eythstrasse 24, 89075 Ulm, Germany
    Blood 109:3595-602. 2007
    ..ADA) deficiency is a systemic metabolic disease that causes an autosomal recessive variant of severe combined immunodeficiency (SCID) and less consistently other complications including neurologic abnormalities...
  96. pmc Radiosensitive severe combined immunodeficiency disease
    Christopher C Dvorak
    Division of Pediatric Blood and Marrow Transplantation, University of California, San Francisco, 505 Parnassus Avenue, M 659, San Francisco, CA 94143 1278, USA
    Immunol Allergy Clin North Am 30:125-42. 2010
    ..Inherited defects in components of the nonhomologous end-joining DNA repair mechanism produce a T-B-NK+ severe combined immunodeficiency disease (SCID) characterized by heightened sensitivity to ionizing radiation...
  97. ncbi Adenosine deaminase-deficient mice generated using a two-stage genetic engineering strategy exhibit a combined immunodeficiency
    M R Blackburn
    Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 273:5093-100. 1998
    ..ADA-deficient mice also exhibited severe pulmonary insufficiency, bone abnormalities, and kidney pathogenesis. These mice have provided in vivo information into the metabolic basis for the immune phenotype associated with ADA deficiency...
  98. ncbi Differential biological role of CD3 chains revealed by human immunodeficiencies
    María J Recio
    Inmunologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain
    J Immunol 178:2556-64. 2007
    ..We propose a CD3delta >> CD3gamma hierarchy for the relative impact of their absence on the signaling for T cell production in humans...
  99. ncbi ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency
    Aisha V Sauer
    San Raffaele Telethon Institute for Gene Therapy HSR TIGET, Milan, Italy
    Blood 114:3216-26. 2009
    ..Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth ..
  100. ncbi Diverse phenotypic and genotypic presentation of RAG1 mutations in two cases with SCID
    Neslihan Edeer Karaca
    Department of Pediatrics, Faculty of Medicine, Ege University, 35100, Bornova, Izmir, Turkey
    Clin Exp Med 9:339-42. 2009
    ....
  101. ncbi Effect of CD3delta deficiency on maturation of alpha/beta and gamma/delta T-cell lineages in severe combined immunodeficiency
    Harjit K Dadi
    Divisions of Immunology and Allergy and the Infection, Immunity, Injury and Repair Program, The Research Institute and The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
    N Engl J Med 349:1821-8. 2003

Research Grants64

  1. Novel SCID rat models for human cell transplantation studies
    Joseph C Ruiz; Fiscal Year: 2010
    ..This mutation is an underlying cause of severe combined immunodeficiency (SCID) in humans...
  2. WI State Public Health Lab Capacity for SCID Screening
    CHARLES DENNIS BROKOPP; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: Project Narrative - relevance to public health Severe combined immunodeficiency (SCID) is an asymptomatic, insidious disease which, untreated, is 100% fatal;SCID can be detected by ..
  3. Identification of Disease-Causing Mutations in SCID Using Exome-Wide Sequencing
    Joseph L Roberts; Fiscal Year: 2010
    ..b>Severe combined immunodeficiency (SCID) is a syndrome characterized by absent T and B lymphocyte function that is uniformly fatal in ..
  4. Inhibition of CCR1/CCR5 mediated angiogenesis and joint destruction by EGCG
    Salah Uddin Ahmed; Fiscal Year: 2010
    ..if EGCG blocks CCR1/CCR5 receptor mediated cell recruitment and tissue invasion in a human RA ST- severe combined immunodeficiency (SCID) mouse chimera...
  5. MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCID
    Rebecca H Buckley; Fiscal Year: 2010
    ..immune reconstitution (16 HLA-identical, investigate identical in patients with severe combined immunodeficiency (SCID) given transplants of rigorously T cell-depleted HLA- The overall goal of the proposed research ..
  6. Mechanism and regulation of DNA end processing in V(D)J recombination and repair
    JoAnn M Sekiguchi; Fiscal Year: 2013
    ..Artemis was initially discovered as the gene inactivated in a human radiosensitive severe combined immunodeficiency syndrome...
  7. Varicella-zoster Virus: Tegument Proteins in Pathogenesis
    Ann Arvin; Fiscal Year: 2012
    ..studying VZV neuropathogenesis by making xenografts of human dorsal root ganglia (DRG) in mice with severe combined immunodeficiency (SCID)...
  8. 3D Structure and Function of CRAC Channels
    STEPHEN BARSTOW LONG; Fiscal Year: 2013
    ..Orai plays an important role in the immune system. A mutation of Orai is a cause of a lethal form of severe combined immunodeficiency in human patients...
  9. Varicella-Zoster Virus: T Cell/Skin Tropism &Immunity
    Ann Arvin; Fiscal Year: 2013
    ..by investigating VZV infection of human skin, T cell and dorsal root ganglia xenografts in the severe combined immunodeficiency (SCID) mouse model...
  10. Inherited Disorders of Lymphocyte Development
    Jennifer M Puck; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Studies of the molecular basis of human severe combined immunodeficiency (SCID) have ushered in a new era of improved diagnosis and treatment of these rare, but serious genetic disorders and also ..
  11. Primary Immune Deficiency Treatment Consortium Annual Scientific Meeting
    Luigi Daniele Notarangelo; Fiscal Year: 2013
    ..studies that would define risk factors, long term outcomes and late effects in children with Severe Combined Immunodeficiency (SCID), Wiskott-Aldrich Syndrome (WAS) and Chronic Granulomatous Disease (CGD) who receive HCT or ..
  12. Regulation of store-operated Ca2+ entry: STIM and ORAI
    Anjana Rao; Fiscal Year: 2013
    ..that mutations in ORAI1 and STIM1 are the underlying cause of at least three instances of hereditary severe combined immunodeficiency in human patients...
  13. Sleeping Beauty-mediated Gene Therapy of X-linked SCID
    Kendra A Hyland; Fiscal Year: 2010
    ..X-linked severe combined immunodeficiency (X-SCID), caused by a mutation in the gene encoding the common ( chain gene ((c) of the receptors for ..
  14. Development of normal and dystrophic canine iPS lines
    COLIN EDWARD BISHOP; Fiscal Year: 2010
    ..These include von Willebrand disease, severe combined immunodeficiency disorder, X-linked Duchenne type muscular dystrophy, pyruvate kinase deficiency, muscle type ..
  15. Improving Primordial Follicle Survival After Transplantation of Cryopreserved Hum
    Kutluk H Oktay; Fiscal Year: 2012
    ....
  16. N-glycosylation as a downstream effector of Interleukin-7
    Haik Mkhikian; Fiscal Year: 2013
    ..defects, causing T-cell-negative (T-), B-cell-negative (B-), natural killer cell-negative (NK-) severe combined immunodeficiency (SCID) in mice...
  17. Xenodiagnosis of Lyme Disease
    Linden T Hu; Fiscal Year: 2012
    ..Repleted ticks will be collected, allowed to molt to their nymphal stage and then fed on severe combined immunodeficiency (SCID) mice. The repleted nymphal ticks and the SCID mice will be tested for the presence of B...
  18. ION CHANNELS AND SIGNALING MECHANISMS IN T LYMPHOCYTES
    Richard S Lewis; Fiscal Year: 2013
    ..to muscle activity, secretion, and motility, and loss of SOC functio in humans leads to a devastating severe combined immunodeficiency with additional myopathy and ectodermal dysplasia...
  19. Humanized Mouse Models of Severe Combined Immunodeficiency
    Sung Yun Pai; Fiscal Year: 2010
    b>Severe combined immunodeficiency (SCID) is a heterogeneous group of fatal congenital disorders characterized by the absence of T lymphocytes...
  20. Molecular basis for ligation of mismatched DNA ends
    Gilbert Chu; Fiscal Year: 2012
    ..However, some of the mutations cause microcephaly and growth delay, while others cause severe combined immunodeficiency. We will determine if such mutations produce distinct biochemical abnormalities in MEnd ligase...
  21. Investigation of herpes simplex virus -1 neurotropism in SCID DRG xenografts
    Ann M Arvin; Fiscal Year: 2010
    ..We will evaluate HSV-1 infection of human dorsal root ganglion (DRG) xenografts in mice with severe combined immunodeficiency (SCID), exploiting the system that we created to investigate varicella- zoster virus (VZV) ..
  22. Foamy Viral Gene Therapy for X-linked Severe Combined Immune Deficiency
    David J Rawlings; Fiscal Year: 2013
    ..foamy virus (FV) vector- based gene replacement therapy for patients who suffer from the inherited severe combined immunodeficiency SCID-X1. The program involves three scientific Projects and four Cores...
  23. Molecular Recognition Studies of the Interleukin-7 Pathway
    SCOTT T WALSH; Fiscal Year: 2012
    ..Under- and over-stimulation of the IL-7 pathway has been implicated in the pathogenesis of a form of severe combined immunodeficiency, autoimmune conditions, coronary artery disease, and several cancers...
  24. Newborn Screening for T-Cell Disorders: Spectrum and Outcomes
    Jennifer M Puck; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Severe combined immunodeficiency (SCID) is a rare, but life-threatening inherited disorder in which infants appear healthy at birth, but lack immunity provided by T and B lymphocytes...
  25. Function of Longus Type IV pili in enterotoxigenic E coli
    OSCAR GOMEZ; Fiscal Year: 2010
    ..ETEC colonization will be evaluated by using a novel human intestine explant-Severe combined immunodeficiency (SCID) mouse model...
  26. Primary Immune Deficiency Treatment Consortium
    Morton Cowan; Fiscal Year: 2013
    ..that can be cured with hematopoietic cell transplantation (HCT), enzyme replacement or gene therapy: severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD)...
  27. Epithelial mesenchymal transition in gastrointestinal homeostasis and disease
    Seema Khurana; Fiscal Year: 2013
    ..together with in vivo studies in the villin-/-, villin+/+, ApcMin/villin-/-;ApcMin/villin+/+, and severe combined immunodeficiency mice (SCID) mice to allow us to unravel the complex question of how EMT is regulated...
  28. Biological Variation in Hemophilia
    JOHN S LOLLAR; Fiscal Year: 2013
    ..stem cell (HSC)-based gene therapy for other congenital disorders, including adrenoleukodystrophy and severe combined immunodeficiency disease, and preclinical studies in a murine hemophilia A model at Emory University, suggest that a ..
  29. Gene Therapy for SCID-X1 using a self-inactivating (SIN) gammaretroviral vector
    David A Williams; Fiscal Year: 2013
    ..Gene therapy for severe combined immunodeficiency has been one of few documented successes but has had significant complications due to development of ..
  30. CryoEM Structural Studies of DNA-PKcs and Nonhomologous End Joining Complexes
    Phoebe L Stewart; Fiscal Year: 2013
    ..Mutations in any of these three components results in radiosensitivity and severe combined immunodeficiency in humans...
  31. Pathway to Accelerate Clinical Development in Gene Transfer: cGMP Vector Core
    Katherine A High; Fiscal Year: 2010
    ..have shown gene therapy's safety and efficacy for a form of congenital blindness and a form of severe combined immunodeficiency disorder...
  32. AAV Vector Integration Frequency and Associated Genome Alterations
    Daniel G Miller; Fiscal Year: 2010
    ..most notable successes of the gene therapy effort is the treatment of several children with X-linked severe combined immunodeficiency syndrome (X-SCID)...
  33. Somatic Mosaicism in the Wiskott-Aldrich Syndrome
    Brian R Davis; Fiscal Year: 2010
    ..g. Wiskott-Aldrich Syndrome [WAS], X-linked Severe Combined Immunodeficiency), Fanconi Anemia, Epidermolysis Bullosa, and Tyrosinemia...
  34. Lentiviral Gene Therapy for Sickle Cell Disease and Immunodeficiency Disorders
    Brian P Sorrentino; Fiscal Year: 2013
    ..for use in patients with sickle cell disease (SCD), Wiscott-Aldrich Syndrome (WAS), and X-linked severe combined immunodeficiency (SCIDXI)...
  35. Sequencing of Newborn Blood Spot DNA to Improve and Expand Newborn Screening
    Robert L Nussbaum; Fiscal Year: 2013
    ..that are not detected by the current T-Cell receptor excision circle assay used for severe combined immunodeficiency screening, and 4) scan 9 genes for variants that are clinically important for drug metabolism and ..
  36. Molecular Recognition Studies of the Interleukin-7 Pathway
    SCOTT T WALSH; Fiscal Year: 2013
    ..Aberrant IL-7 signaling has been implicated in severe combined immunodeficiency, autoimmune conditions, and cancers...
  37. DEVELOPMENT OF NEW SCID MOUSE MODELS FOR AIDS RESEARCH
    Leonard Shultz; Fiscal Year: 1999
    ..The lack of functional lymphocytes in C.B- 17 mice homozygous for the severe combined immunodeficiency (scid) mutation has enabled limited engraftment with human lymphocytes and hematopoietic stem cells...
  38. MECHANISMS OF ANTIFOLATE EFFICACY IN ARTHRITIS
    Sarah Morgan; Fiscal Year: 2000
    ..The information obtained from the proposed research will enhance the understanding of the biochemical action of antifolates/antimetabolites that are effective in the treatment of human and animal arthritis. ..
  39. CANCER PATIENTS IMMUNE RESPONSES STUDIED IN SCID MICE
    Dorothee Herlyn; Fiscal Year: 1992
    ..Mice with severe combined immunodeficiency (SCID) may provide such a model...
  40. METVAN: A Novel Anticancer Agent
    OSMOND D CRUZ; Fiscal Year: 2003
    ..exhibits significant antitumor activity, delays tumor progression and prolongs survival time in severe combined immunodeficiency (SCID) mouse xenograft models of human malignant glioblastoma and breast cancer...
  41. MURINE MODEL OF HIV INFECTION OF HUMAN BRAIN
    Cristian Achim; Fiscal Year: 1999
    ..neural cells aggregate and form "brain microspheres" which are then transplanted into the crania of severe combined immunodeficiency (SCID) mice...
  42. Gene Therapy for Purine Nucleoside Phosphorylase Deficiency (PNP)
    Kevin Baker; Fiscal Year: 2007
    ..The first was a French trial of retroviral gene therapy for X-linked severe combined immunodeficiency (SCID), in which bone marrow cells from children deficient in the common gamma-chain for several ..
  43. ADOPTIVE TRANSFER OF CD8+ CTLS TO CONTROL EIAV
    ROBERT MEALEY; Fiscal Year: 2001
    ..Work using foals affected with severe combined immunodeficiency (SCID) has shown that lymphocyte responses are required to terminate the viremia following acute ..
  44. MODEL FOR EMERGENCE OF PARVOVIRUS B19 VIRULENCE
    STANLEY NAIDES; Fiscal Year: 1999
    ..The applicants have made the hypothesis that hepatotropic B19 bariants express mutant NS1 with increased cytotoxicity. The investigators will employ molecular virological and cell culture methods to test their hypotheses. ..
  45. Adenosine Deaminase, Adenosine Signaling and Disease
    RODNEY KELLEMS; Fiscal Year: 2006
    ..However, despite many years of investigation the molecular basis of the severe combined immunodeficiency resulting from ADA deficiency is not understood...
  46. ADENOSINE DEAMINASE DEFICIENCY
    Linda Thompson; Fiscal Year: 2007
    Mutations in the gene for adenosine deaminase (ADA) cause severe combined immunodeficiency in humans. ADA-deficient patients exhibit a profound lymphopenia and are susceptible to a wide array of infectious agents...
  47. Effects of NefM-1 peptide on primary and metastatic colorectal cancer xenografts
    Harvey L Bumpers; Fiscal Year: 2013
    ..Aim-I will assess the capacity of NefM-1 to inhibit, in severe combined immunodeficiency (SCID) mice, the growth and angiogenesis of various human CRC xenografts derived from surgical ..
  48. IL2 RECEPTORS--ANALYSIS OF ASSEMBLY AND SIGNALING
    Warner Greene; Fiscal Year: 1999
    ..while mutations in the gamma gene have been identified as the genetic defect underlying X- linked severe combined immunodeficiency disease (X-SCID)...
  49. ROLE OF DNA DEPENDENT PROTEIN KINASE IN DNA REPAIR
    Paul Labhart; Fiscal Year: 2002
    ..Some of these radiation sensitive organisms and cells display at the same time severe combined immunodeficiency (SCID)...
  50. Anti-Apoptotic Signaling by the IL-2/15 Receptor
    SARAH GAFFEN; Fiscal Year: 2006
    ..by three other cytokine receptors, and consequently, a genetic deficiency in gamma-c causes X-linked severe combined immunodeficiency. The goal of this project is to explore mechanisms by which the IL-2 and IL-I5 receptors deliver ..
  51. CMV LABYRINTHITIS INDUCED IN IMMUNODEFICIENT SCID MICE
    NIGEL WOOLF; Fiscal Year: 2004
    ..provided by applicant):Experimental cytomegalovirus (CMV) labyrinthitis and encephalitis in SCID (severe combined immunodeficiency) mutant mice provides a useful model for the auditory system pathologies and hearing loss observed in ..
  52. Vector Insertion and Mutagenesis in Human Hematopoiesis
    Christof von Kalle; Fiscal Year: 2007
    ..has been used to correct genetic defects most successfully in patients with potentially fatal human severe combined immunodeficiency disease (SCID)...
  53. IMMUNE CELL COOPERATION IN HUMAN HAPLOIDENTICAL CHIMERA
    JOSEPH ROBERTS; Fiscal Year: 1990
    ..complex (MHC) restriction of antigen recognition by genetically donor T cells of patients with severe combined immunodeficiency disease engrafted with parental haploidentical bone marrow stem cells...
  54. THE REGULATION OF PURINE BIOSYNTHESIS IN E. COLI K12
    John Smith; Fiscal Year: 1991
    ..These include Lesch-Nyhan disease, severe combined immunodeficiency and most recently discovered, a defect in adenylosuccinate lyase that results in autism...
  55. Strategies Against HPV Related Genital Diseases in Women
    Bradley Monk; Fiscal Year: 2006
    ..D., Dr. Monk will evaluate co-carcinogens and anti-viral agents in a recently described severe combined immunodeficiency mouse model using implanted human HPV infected epithelium, cervical intraepithelial neoplasia (CIN)...
  56. MECHANISMS OF ALLOGENEIC STEM CELL EDUCATION IN SCID
    Rebecca Buckley; Fiscal Year: 2003
    ..proposed research is to investigate the mechanisms of allogeneic stem cell education in patients with severe combined immunodeficiency (SCID) given transplants of rigorously T cell-depleted bone marrow cells without pre-transplant ..
  57. HLA RELATIONSHIPS OF PREGNANCY, CHIMERISM & AUTOIMMUNITY
    J Nelson; Fiscal Year: 1999
    ..Persistent maternal cells have been found in the circulation of infants with severe combined immunodeficiency. However, studies have not examined whether maternal cells persist at low levels in apparently normal ..
  58. PHOSPHONIUM-TAXOL CONJUGATES AS ANTITUMOR DRUGS
    Xiaoen Wang; Fiscal Year: 1993
    ..that taxol inhibits the metastatic spread of a PC-3 human prostate tumor cell subline in a SCID (severe combined immunodeficiency) model, and inhibits processes associated with metastasis (attachment, migration, protease secretion) ..
  59. Hematopoietic Stem Cell Transposon Therapy for Severe Combined Immunodeficiency
    Jakub Tolar; Fiscal Year: 2009
    DESCRIPTION (provided by applicant): Our goal, and the main challenge in the treatment of severe combined immunodeficiency (SCID) today, is to develop a robust alternative to allogeneic hematopoietic stem cell (HSC) transplantation and ..
  60. CONTROL OF IA ANTIGEN EXPRESSION
    SANTA ONO; Fiscal Year: 1999
    ..of certain autoimmune diseases and lack of expression of these molecules is the cause of the severe combined immunodeficiency disorder: Bare Lymphocyte Syndrome...
  61. COCAINE SMOKING EFFECTS ON LUNG IMMUNITY & HOST DEFENSE
    Michael Roth; Fiscal Year: 2006
    ..abstract_text> ..
  62. Chemoresistance and Stem Cell Selection
    David A Williams; Fiscal Year: 2010
    The success of the gene therapy trial in treatment of severe combined immunodeficiency (SCID) provides evidence of the power and utility of in vivo selection of transduced hematopoietic cell populations...
  63. TRANSLATIONAL CONTROL OF ADENOSINE DEAMINASE
    Elaine Chottiner; Fiscal Year: 1990
    ..information which could aid in the development of ADA expression vectors for gene transfer therapy in severe combined immunodeficiency syndrome...
  64. GENETIC ANALYSIS OF IMMUNODEFICIENCY DISEASES
    Jennifer Puck; Fiscal Year: 1992
    ..diseases are inherited in an X linked recessive fashion, including the most common forms of severe combined immunodeficiency disease (XSCID) and agammaglobulemia (XLA), as well as Wiskott Aldrich syndrome (WA), X linked ..